The present invention, in some embodiments thereof, relates to material science and, more particularly, but not exclusively, to nano- and micro-structures composed of self-assembled peptide nucleic acids (PNAs), to processes of generating same and to uses thereof.
Molecular self-assembly is the spontaneous organization of molecular units into ordered structures as a result of local interactions among the molecules themselves, without any external intervention. The concept of self-assembly is a widely applied approach in the field of nanotechnology for the bottom-up fabrication of novel nanoscopic and macroscopic elements from natural or synthetic building blocks.
Peptide building blocks have been widely used in the past decade or so for forming well-organized assemblies. The arrangement into ordered structures involves a combination of non-covalent interactions such as van der Waals, electrostatic, hydrophobic and aromatic m-stacking interactions as well as hydrogen and coordination bonds. The synergy between these weak individual forces often leads to the formation of ordered structures with notable morphological, mechanical and other physical features.
Structural DNA nanotechnology is derived from the specificity of the hydrogen bonding interactions between complementary Watson-Crick base pairs, which enables the recognition and highly selective binding of complementary strands. These features were recognized as useful for the construction of ordered structures via self-assembly and have been exploited to rationally design various structures including nanowires, nanogrids and three-dimensional well-ordered shapes. See, for example, Winfree et al. Nature, 1998. 394(6693): p. 539-544; He et al. Nature, 2008. 452(7184): p. 198-201; and Seeman, N.C., Trends in biotechnology, 1999. 17(11): p. 437-443.
Both peptides and DNA are susceptible to enzymatic degradation and are also typically characterized by chemical sensitivity to temperatures and pH. These features limit the use of peptide- and DNA-based assemblies.
Peptide nucleic acid (PNA) is an artificially synthesized polymer that was first described by Peter Nielsen's and Ole Buchardt's research groups in 1992. In its basic form, it is an oligonucleotide analog in which the phosphate ribose ring of DNA is replaced by a polyamide backbone composed of repeating N-(2-aminoethyl)glycine units linked by peptide bonds. Methylene carbonyl linkages connect between the central amine of the backbone and the various nucleobases. The configuration and the intramolecular distances between neighboring bases, as imposed by the peptide-like backbone, are equal to those in natural nucleic acids.
Background art FIG. 1 presents the general chemical structure of PNA, compared to that of DNA [Lundin et al. Advances in genetics, 2006. 56: p. 1-51].
PNAs have been used in the formation of ordered nano- and micro-sized self-assembled architectures, yet only as a template or as a conjugate to the self-assembled structure in order to gain specific recognition properties.
Thus, to date, PNAs are utilized in the context of material science mainly as a molecular probe for diagnostics and detection.
The following approaches have been employed in this regard: (1) PNA-based self-assembled monolayers on solid surfaces (nanoparticles or bulk materials) [see, for example, Harris, J. L. and N. Winssinger, Chemistry-a European Journal, 2005. 11(23): p. 6792-6801; Briones et al. Journal of Molecular Catalysis A: Chemical, 2005. 228(1): p. 131-136; Liu et al. Biosensors and Bioelectronics, 2007. 22(12): p. 2891-2897; Mateo-Marti et al. Biosensors and Bioelectronics, 2007. 22(9): p. 1926-1932; Mateo-Marti et al. Langmuir, 2005. 21(21): p. 9510-9517; Mateo-Marti et al. Surface Science, 2007. 601(18): p. 4195-4199; and Singh et al. Bioelectrochemistry, 2010. 79(2): p. 153-161]; (2) carbon nanotubes (CNTs) covalently and non-covalently conjugated to PNAs [Williams et al. Nature, 2002. 420(761): p. 38; Kerman et al. Nanobiotechnology, 2005. 1(1): p. 65-70; Maehashi et al. Japanese journal of applied physics, 2004. 43: p. 1558; and Rajendra et al. Chemistry-a European Journal, 2005. 11(16): p. 4841-4847]; and (3) self-organized nanostructures including fibers [Guler et al. Bioconjug Chem, 2005. 16(3): p. 501-503; two-dimensional arrays [Lukeman et al. Chemical Communications, 2004(15): p. 1694-1695]; microgels [Cao et al. Journal of the American Chemical Society, 2003. 125(34): p. 10250-10256]; and films and capsules [Becker et al. Macromolecular bioscience, 2010. 10(5): p. 488-495].
Additional background art includes Achim et al., “Peptide Nucleic Acids” in Wiley Encyclopedia of Chemical Biology, 2008, pp. 1-10, Bonifazi et al., Artificial DNA: PNA & XNA 3:3, 112-122, July-December 2012, and U.S. Pat. No. 8,309,514.